The present invention relates to the use of saturated monocyclic or bicyclic terpenes for the treatment of inflammatory diseases. It is particularly concerned with the use of saturated monocyclic terpenes for the treatment of steroid-requiring inflammatory diseases exacerbated by infection, such as, for example, bronchial asthma.
Acute and/or chronic inflammatory or acute allergic and/or chronic allergic inflammatory lesions are characterized by inflammatory infiltration of various organ systems by monocytes/macrophages, eosinophils, basophils and neutrophils, granulocytes, mast cells and thrombocytes. The degree of inflammatory activity correlates with the influence of these inflammatory cells in organ tissue, which causes damage to the organ concerned. These processes are a familiar feature in primary inflammatory diseases of the airways, the intestine and the articular cartilage in rheumatoid arthritis. Since the primary cause triggering most chronic inflammatory diseases is not known, these diseases can only be alleviated by nonspecific suppression of the inflammation stimulus. In an appropriate genetic predisposition or in the presence of environmental noxae, the reaction of the body to the exogenous noxae can be inhibited prophylactically by nonspecific suppression of the inflammation stimulus before the manifestation of disease symptoms.
At the level of the cell, the further migration of inflammatory cells into an area of inflammation can be reduced by inhibiting chemotactic factors. This leads to the inflammatory activity subsiding with decline of the morphological and functional disorders of the organ system concerned, an effect which is typically mediated by immunosuppressants, e.g. corticosteroids. This group of agents is known to have an activity profile which comprises a strong anti-inflammatory effect, but is only poorly tolerated since it causes severe side effects, namely osteoporosis, gastric and duodenal ulcers, steroid purpura or lymphopenia.
Corticosteroids are known to inhibit the activity of phospholipase and cytokines in various inflammatory cells. After inhibition of the phospholipase activity, the release of arachidonic acid from the phospholipid stores in the cell membrane is inhibited. Arachidonic acid is known to be an important substrate for the formation of various mediators.
The actual inhibitory action on inflammation is mediated by inhibition of cytokine production and via a reduced production of arachidonic acid. The latter is the precursor for the formation of potent chemotactic metabolites of the 5-lipoxygenase pathway (leukotrienes) and the cyclo-oxygenase pathway (prostaglandins, thromboxane) with a constrictor action on smooth muscle cells. Owing to the persistent suppression, especially of mediators of the 5-lipoxygenase metabolic pathway, the need for systemically active corticosteroids is therefore reduced and the activity of the inflammatory process is suppressed with diminishing infiltration with inflammatory cells.
For this reason, the disease course of various acute, chronic or allergic inflammations can be favorably influenced by nonspecific inhibition of inflammation.